1. Field of the Invention
This invention relates to retinoic acid-containing compositions. More particularly, this invention relates to retinoic acid-containing topical compositions for use in treating, inter alia, acne vulgaris in humans. The compositions of this invention exhibit reduced skin irritation but undiminished effectiveness as compared to prior art retinoic acid-containing topical compositions.
2. Description of Related Prior Art
Retinoic acid, or 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid, sometimes known as all-trans retinoic acid, vitamin A acid or tretinoin), has the structural formula: ##STR1##
Retinoic acid and like compounds are keratolytic agents, and have been used topically in the treatment of acne vulgaris; see, for example, Kligman U.S. Pat. No. 3,729,568 and Marks U.S. Pat. No. 4,247,547, issued Apr. 24, 1973 and Jan. 27, 1981, respectively.
Retinoic acid and compositions containing it have also been used topically to retard and ameliorate photoageing of skin, especially facial skin, and to retard and reverse the effects of senile keratosis; see, for example, Kligman U.S. Pat. No. 4,603,146, issued Jul. 29, 1986.
Moderate to severe skin irritation can result from the use of retinoic acid and topical prior art compositions containing it for such purposes.
Chess, et al. U.S. Pat. Nos. 4,971,800; 5,045,317 and 5,051,260, issued Nov. 20, 1990, Sep. 3, 1991 and Sep. 24, 1991, respectively, all assigned to The Regents of the University of California and exclusively licensed to the assignee of the present application, disclose compositions comprising hydroxy-terminated urethane penetration enhancing compounds represented by the general formula: ##STR2## wherein R represents an alkylene or alkenylene radical, generally one containing from about one to about 20 carbon atoms, such as methylene, trimethylene and dimethyltrimethylene radicals, and in the case of the alkenylene radicals, one having between one and about 3 double bonds, or a cycloalkylene or cycloalkenylene radical, generally one containing from about 5 to about 10 carbon atoms, such as cyclopentylene, cyclohexylene and cyclohexenylene radicals, or a mononuclear or fused ring arylene radical, generally one containing from about 6 to about 10 carbon atoms, such as phenylene or naphthylene, all of which can be unsubstituted or substituted, e.g., with alkyl groups, generally ones containing up to about 6 carbon atoms, aryl groups which may be substituted with amine moieties, nitro, lower (1-6 C) alkyl, lower (1-6 C) alkoxy, lower (1-6 C) alkoxy-substituted lower (1-6 C) alkyl, halogen, and the like. R.sup.1 represents the same or different alkylene or alkenylene radicals, generally ones containing from about 2 to 6 carbon atoms, such as --CH.sub.2 CH.sub.2 -- and --CH.sub.2 CH.sub.2 CH.sub.2 --, and in the case of the alkenylene radicals, ones typically having one or two double bonds; m is an integer selected so as to provide an .paren open-st.O--R'.paren close-st. moiety having a molecular weight of from about 40 to about 6,000, more typically from about 400 to about 2,000, and n and n' are the same or a different integer of from 0 to 30, inclusive, correlated with m so as to provide penetration enhancers for delivering pharmacologically active agents (i.e., "drugs" or "medicaments") to and through the skin said penetration agents having a molecular weight of up to about 60,000, more typically from about 220 to about 37,000, and preferably from about 1,000 to about 10,000-15,000.